Note: a dashed line (without arrowheads) between two compound names is meant to imply that the two names are just different instantiations of the same compound -- i.e. one may be a specific name and the other a general name, or they may both represent the same compound in different stages of a polymerization-type pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: N-acetylneuraminate catabolism, sialic acid degradation
|Superclasses:||Degradation/Utilization/Assimilation → Carboxylates Degradation|
Some taxa known to possess this pathway include : Abiotrophia defectiva , Clostridium perfringens [Walters99], Clostridium perfringens 13 [Pelissier14], Clostridium perfringens A99 [Kruger01], Escherichia coli K-12 substr. MG1655 , Streptococcus anginosus , Streptococcus constellatus , Streptococcus gordonii , Streptococcus intermedius , Streptococcus mitis , Streptococcus oralis , Streptococcus sanguinis
Expected Taxonomic Range: Bacteria
Several viridans streptococci, such as Streptococcus oralis, are able to enter the bloodstream through dental caries and cause several serious infections, including endocarditis, brain abscesses and, in immunocompromised patients, septicaemia [Straus77, Ochiai99, Byers99].
The exact mechanisms by which these organisms proliferate in vivo are unknown. One of the potential sources of fermentable carbohydrate are host-derived sialic acids such as N-acetylneuraminate, which is present in serum, and can be liberated from glycoproteins and other sialoglyoconjugates via the action of sialidases [Beighton90, Byers00].
Several species of the viridans streptococci, including Abiotrophia defectiva, Streptococcus anginosus, Streptococcus constellatus, Streptococcus gordonii, Streptococcus intermedius, Streptococcus mitis, Streptococcus oralis and Streptococcus sanguinis are able to utilize N-acetylneuraminate as a sole carbon source, independently of sialidase production [Byers96]. The major end products of N-acetylneuraminate metabolism in these organisms are formate, acetate and ethanol.
A transport system for N-acetylneuraminate was characterized in Streptococcus oralis [Byers99]. This system followed typical Michaelis-Menten kinetics, with a Km of 21.0 μM and a Vmax of 2.65 nmoles/min/mg of dry cell mass.
The pathway for the degradation of N-acetylneuraminate has been studied in viridans streptococci, and its first part is essentially identical to the pathway found in Escherichia coli K-12 (see superpathway of N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminate degradation). The first step of the pathway consists of splitting of N-acetylneuraminate into N-acetyl-β-D-mannosamine and pyruvate, catalyzed by the enzyme N-acetylneuraminate lyase. N-acetyl-β-D-mannosamine is then phosphorylated to N-acetyl-D-mannosamine 6-phosphate. Next the acetyl group is removed (by N-acetylglucosamine-6-phosphate deacetylase), followed by removal of the ammoium group (by glucosamine-6-phosphate deaminase), resulting in formation of β-D-fructofuranose 6-phosphate, which enters glycolysis for substrate level phosphorylation.
In oral streptococci the end product of glycolysis, pyruvate, can be fermented into either (S)-lactate or to formate, acetate and ethanol. When grown on N-acetylneuraminate no lactate is produced, and only the later three products are observed [Byers96].
Subpathways: glycolysis II (from fructose 6-phosphate) , N-acetylglucosamine degradation I , N-acetylneuraminate and N-acetylmannosamine degradation I , pyruvate fermentation to ethanol I , pyruvate fermentation to acetate IV , acetate formation from acetyl-CoA I
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